[unreadable] In contrast to the hemodynamic and glucose/oxygen metabolic consequences of altered electrical activity, the neurochemical, neuroenergetic and metabolic basis of brain activation at the neuroglial level is not as well researched in vivo, It is our long-term objective to obtain a comprehensive assessment of cerebral carbohydrate metabolism as it relates to increased brain activity and neuronal/glial compartmentation in the intact brain. Our central hypothesis is that glutamate neurotransmission represents a fraction of total brain glucose consumption and that the malate-aspartate shuttle is a major rate-determining mechanism in oxidative brain glucose metabolism. The overall strategy is to measure glial and neuronal energy metabolism, malate-aspartate shuttle (MAS) activity, brain glycogen metabolism and glucose transport in rats, hibernating squirrels and humans using an emerging new tool, state-of-the-art 13C and 1H NMR spectroscopy at ultra-high magnetic fields, combined with functional MR imaging. The project represents the continuation of our ongoing effort, the outcome of which will be to provide an unprecedented comprehensive understanding of the neurochemical basis of brain function in vivo at the cellular level, with the potential to characterize disease progression long before structural changes are evident in many neurodegenerative and other diseases of the brain, where glutamate has been implicated. [unreadable] [unreadable]